Chronic graft vs. host disease and hypogammaglobulinemia predict a lower immunological response to the BNT162b2 mRNA COVID-19 vaccine after allogeneic hematopoietic stem cell transplantation.

OBJECTIVE: Due to the high mortality rate of COVID-19, the assessment of BNT162b2 SARS-CoV-2 mRNA vaccine (Pfizer-BioNTech) efficacy in allogeneic hematopoietic stem cell transplant (HSCT) recipients is mandatory. PATIENTS AND METHODS: We conducted a single-center pilot study with the main objective of evaluating the immunogenicity of the BNT162b2 mRNA vaccine in 31 hematological patients who underwent hematopoietic stem cell transplantation within the previous 12 months and/or were affected by chronic graft-vs.-host-disease (cGVHD), by the assessment of antibody levels at 30-45 days after the second dose of vaccine. RESULTS: After the second dose of vaccine, 23 out of 31 patients (74%) showed a positive immune response. The presence of severe cGVHD or Ig deficiency identified 7 out of 8 (85%) of non-responders. The median absolute cluster of differentiation 19 (CD19) count was significantly lower in non-responders vs. responders (109/µl vs. 351/µl). Underlying pathology, comorbidities, type of donor, time intervals from transplant and cluster of differentiation 3/cluster of differentiation 4/cluster of differentiation 8 (CD3/CD4/CD8) subsets were not significantly associated with an effective immune response to vaccination. CONCLUSIONS: Despite the limited sample of patients enrolled, our findings suggest that hypogammaglobulinemia and cGVHD could be associated with poor humoral response to the BNT162b2.

alpha-Melanocyte-stimulating hormone during human perinatal life.

To obtain information on human pituitary intermediate lobe activity throughout the perinatal period, plasma alpha MSH immunoreactivity (IR) was measured in 106 newborns at delivery and during the first week of postnatal life. Subjects were divided into groups according to gestational age at birth, mode of parturition, and antenatal state of health. Plasma alpha MSH IR decreased progressively from severe preterm to fullterm neonates born by vaginal delivery (VD; P < 0.001) or cesarean section (CS) with and without prenatal distress (P < or = 0.001 in both cases). alpha MSH IR was due, in all studied conditions, to three major forms: desacetyl alpha MSH, alpha MSH, and diacetyl alpha MSH. Desacetyl alpha MSH was always the most represented form, but it decreased from 75-80% of the total in severe premature to 40-45% in mature infants. In term neonates, total alpha MSH IR values were higher in subjects born by normal VD than by elective CS (P < or = 0.05), in complicated than in normal VD (P < or = 0.01), and in CS performed because of fetal distress than in elective CS (P < or = 0.01). No significant difference was detectable in mature subjects in the percentages of the three alpha MSH forms in relation to the mode of delivery and fetal state during antenatal life or at parturition. Twelve hours after birth, total alpha MSH IR significantly decreased in all groups of term newborns, reaching a plateau of 0.8-1.4 pmol/L. In premature infants, similar concentrations were detectable by the fourth postnatal day. We conclude that 1) alpha MSH IR intermediate lobe secretion progressively decreases throughout the third trimester of pregnancy; 2) stress, including that pertinent to parturition, stimulates alpha MSH IR release; and 3) pituitary intermediate lobe activity declines shortly after birth independently of the maturity reached by the fetus, the mode of parturition, and the presence of antenatal chronic distress, although the process is slightly retarded in premature newborns.

Blood pressure responses to acute or chronic captopril in mice with disruption of bradykinin B2-receptor gene.

OBJECTIVE: To evaluate the role of kinins in the hypotensive response to angiotensin converting enzyme inhibition, we compared the blood pressure effects induced by acute or chronic captopril administration in a mouse strain (Bk2r-/-) with disruption of the bradykinin B2 receptor gene and in wild-type controls (J129 Sv mice). A second aim was to determine whether Icatibant, a selective bradykinin B2-receptor antagonist, prevented the blood pressure changes induced by acute captopril administration in Swiss, c57/B16, J129 Sv and Bk2r-/- mice. METHODS AND RESULTS: Under basal conditions, tail-cuff systolic blood pressure (SBP) and intra-arterial mean blood pressure (MBP) were higher in Bk2r-/- than in J129 Sv (SBP: 132+/-2 versus 113+/-3 mmHg; MBP: 144+/-6 versus 122+/-10 mmHg, P< 0.05 for both comparisons). Acute captopril administration (1 mg/kg body weight, intra-arterially) reduced the MBP of Bk2r-/- and J129 Sv by 36+/-8 and 31+/-7 mmHg, respectively. Swiss and c57/B16 mice showed similar decreases in MBP following captopril. Pretreatment with Icatibant (10 nmol/kg body weight, intra-arterially) did not influence the MBP responses to acute captopril in all the strains. Chronic administration of captopril (approximately 120 mg/kg body weight per day for 2 weeks in drinking water) reduced SBP in either Bk2r-/- or J129 Sv. The magnitude of this response was higher in Bk2r-/- than in J129 Sv (65+/-3 versus 47+/-4 mmHg, respectively, P < 0.01). CONCLUSIONS: Our results suggest that endogenous kinins do not participate in the hypotensive response to angiotensin converting enzyme inhibition in mice; in Bk2r-/-, the exaggerated blood pressure response to chronic captopril appears to be attributable to interference with unbalanced vasoconstrictor action of the renin-angiotensin system.

Prenatal diagnosis of beta thalassemia: experience with 133 cases and the effect of fetal blood sampling on child development.

Prenatal diagnosis was attempted in 133 pregnancies at risk for beta thalassemia (132 cases) or sickle-cell beta 0 thalassemia (1 case). Of these, 76 couples requested diagnosis because they already had children affected with homozygote beta thalassemia (72 cases) or beta+ thalassemia (4 cases). The others were probably at risk for beta 0 thalassemia since this is by far the predominant thalassemia type in Sardinia. Sufficient fetal blood for analysis was obtained by placental aspiration at 18--24 weeks gestation in 130 cases. Ten fetal losses occurred. The pregnancies were followed and no relevant complications were seen. Of the newborns delivered, 45 were followed from birth with particular attention to congenital malformation, neurological, growth, and maturity assessement. No major adverse effect of placentocentesis on child growth and development was observed. Placental samples were analyzed by globin chain synthesis analysis on carboxylmethylcellulose columns. When the placental samples contained more than 20% maternal red cells, fetal red cell enrichment was carried out by anti-i (53 cases) or anti-AB (2 cases) differential agglutination or NH4Cl-NH4HCO3 differential lysis of maternal cells (17 cases). Of the 130 cases, 32 fetuses had no beta-chain radioactivity and one had a beta/gamma ratio of 0.005. These were presumed to be homozygous and all but one were electively aborted. Absence of beta-chain radioactivity was confirmed in 10 abortuses with suitable cord blood samples. A total of 91 infants have been born and are nonhomozygous. Genotype assessment at 6 months after birth in 33 infants showed that there was only a slight overlap between the ranges of normal (0.095 +/- 0.016) and heterozygous (0.05 +/- 0.01) fetal beta/gamma globin chain synthesis ratios.

[The presence of nucleotide sequences of the hepatitis B virus in peripheral lymphocytes of patients with acute hepatitis B]. / Presenza di sequenze nucleotidiche del virus dell'epatite B nei linfociti periferici di pazienti con epatite acuta di tipo B.

Hepatitis B virus (HBV) DNA sequences were assessed in 26 patients with acute type B hepatitis, using dot-blot hybridization technique from peripheral blood mononuclear cells (PBMC), during different phases of the illness. At clinical presentation, 15% of patients showed HBV-DNA sequences in PBMC, while serum HBV-DNA was detected in 58% of patients. During clinical improvement 50% of patients had HBV-DNA in PBMC but only 11.5% were positive for serum HBV-DNA. Twenty-three (88.5%) patients recovered and cleared HBV-DNA from serum and from PBMC; three (11.5%) patients with acute hepatitis progressing to chronicity showed persistently HBV-DNA sequences in serum and in PBMC. In conclusion, our study shows that HBV-DNA sequences may be found in PBMC, transiently in patients with acute hepatitis followed by recovery, persistently in patients with acute hepatitis progressing to chronicity.

[Induction of therapeutic abortion with intravenous administration of prostaglandin F 2-alpha]. / Induzione dell'aborto terapeutico con prostaglandina F2 alpha per via endovenosa.

PIP: 24 women, aged 22-41, with parity 0-4, and between the 8-24 week of pregnancy, underwent therapeutic termination of pregnancy by intravenous injection of prostaglandin F2 alpha. There were 23 complete abortions in a relatively short time. No serious complications were observed, although most patients suffered from nausea, vomiting, and diarrhea. This technique proved to be much safer and effective than other techniques previously experimented.^ieng

Ultrasound monitoring of gestosis polycentric study.

In polycentric research we studied 62 selected cases of gestosis to evaluate which symptom is greatly correlated with the deficit of fetal growth. According to us, the earlier the syndrome appearance the clearer the deficit of fetal growth.

Nanocrystals as tool to improve piroxicam dissolution rate in novel orally disintegrating tablets.

In this paper, orally disintegrating tablets (ODT) were prepared using nanocrystal formulations in order to optimise dissolution properties of lipophilic, poorly soluble drug piroxicam (PRX). Different nanocrystal formulations were prepared using a high pressure homogenisation technique and poloxamer 188 as stabiliser. Characterisation of PRX nanocrystal ODT was carried out by infrared spectroscopy (FTIR), X-ray powder diffractometry (XRPD), differential scanning calorimetry and photon correlation spectroscopy. Dissolution study of PRX ODT was performed in distilled water (pH 5.5) and was compared to that of PRX coarse suspension ODT, PRX/poloxamer 188 physical mixture and bulk PRX samples. The XRPD and FTIR studies demonstrated that the homogenisation process led to a polymorphic transition from form I (bulk commercial PRX) to form III and monohydrate form of the nanocrystals. All ODT formulations prepared using PRX nanosuspensions showed a higher PRX dissolution rate compared with the ODT prepared with the coarse PRX. Since the solubility of the different PRX polymorphic forms increased only slightly from bulk PRX (form I) to monohydrate, form II and form III, we can conclude that the improvement in PRX dissolution rate is mainly caused by the increased surface-to-volume ratio due to the submicron dimension of the drug particles.